Chemical and biological analysis of 4-acyloxy-3-nitrocoumarins as trypanocidal agents
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Chagas disease is the most widespread contagious tropical disease in Latin America, being an important public health problem. Treatments against this disease are still very ineffective, presenting several side effects. Therefore, the search for alternative therapeutic solutions is urgent. In the present work, we evaluate the trypanocidal activity and the mechanism of action of a select series of synthetic 4-acyloxy-3-nitrocoumarins. All the coumarin derivatives showed moderate trypanocidal activity in trypomastigotes, along with low cytotoxicity. In addition, compound 1 decreased the number of infected Vero cells in an intracellular T. cruzi model. Electron spin resonance and electrochemical studies showed the formation of nitro radical anions. The Fukui index provided additional information to elucidate the proposed reduction mechanism. Furthermore, in vitro radical formation studies demonstrated the potential of these compounds to achieve higher concentrations of intracellular free radicals, proposing oxidative stress as a possible trypanocidal mechanism. Furthermore, no correlation was observed between the diffusion of these compounds, which shows that lipophilicity is not a predominant factor for activity.
Portuguese Foundation for Science and Technology European Commission CEECIND/02423/2018 UIDB/00081/2020 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1190340 REDES170126 1170126 3190449 ANID/PCI REDES 170126 Xunta de Galicia (Galician Plan of Research, Innovation and Growth 2011-2015, Plan I2C) ED481B 2014/086-0 ED481B 2018/007
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Quote ItemArabian Journal of Chemistry (2021) 14, 102975
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